High-grade Salivary Gland CarcinomaPhase 2NCT00095563
Lapatinib in Treating Patients With Recurrent and/or Metastatic Adenoid Cystic Cancer or Other Salivary Gland Cancers
A Phase 2 study testing lapatinib ditosylate and laboratory biomarker analysis in people with High-grade Salivary Gland Carcinoma and High-grade Salivary Gland Mucoepidermoid Carcinoma, run by National Cancer Institute (NCI) at 1 site in Canada.
Trial summary
Phase II trial to study the effectiveness of lapatinib in treating patients who have recurrent and/or metastatic adenoid cystic cancer or other salivary gland cancers. Lapatinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High-grade Salivary Gland Carcinoma, High-grade Salivary Gland Mucoepidermoid Carcinoma, Low-grade Salivary Gland Carcinoma
- What is being tested?
- lapatinib ditosylate and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2004to Jun 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically documented or cytologically confirmed adenoid cystic, or other malignant salivary gland carcinomas of major or minor salivary gland origin; all patients must have either EGFR and/or erbB2 expressing tumors (for definitions of EGFR and erbB2 expression to be enrolled in this study; EGFR and erbB2 expression will be determined using archival paraffin samples for all study patients where possible; if these samples are unavailable then patients must undergo a biopsy to determine their EGFR and erbB2 status
- Patients must have recurrent and/or metastatic disease that is progressive and not amenable to surgery or curative radiotherapy; progressive disease is defined as one of the following occurring within 6 months of study entry:
- At least a 20% increase in radiologically or clinically measurable disease
- Appearance of any new lesions or
- Deterioration in clinical status
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
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- Patients may have had unlimited prior therapy; however, there must be at least a 4 weeks' interval between any chemotherapy (6 weeks for nitrosoureas or mitomycin C), radiotherapy or surgery and study enrollment; exceptions may be made however, for low dose, non-myelosuppressive radiotherapy - please contact the Principal Investigator (Dr. L. Siu) PRIOR to registration if questions arise about the interpretation of this criterion; for patients who received local therapy prior to study entry, there must be either progression of measurable disease documented within the treatment field, or must have measurable disease outside the treatment field prior to study entry
- Life expectancy of greater than 12 weeks
- ECOG performance status 0,1, or 2
- Leukocytes >= 3,000/uL
- Absolute neutrophil count >= 1,5000/uL
- Platelets >= 100,000/uL
- Total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) =< 2.5 x institutional upper limit of normal
- Creatinine within normal institutional limits OR
- Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram or MUGA scan: Note that baseline and on treatment scans should be performed using the same modality and preferably at the same institution
- Must be willing and able to undergo tumor biopsy once before and once during investigational therapy; patients must have tumor lesions accessible for biopsy for correlative studies; the decision regarding the safety of doing a biopsy will be made by an interventional radiologist rather than the investigator and must be documented in writing; in cases where there is a medical contraindication to tumor biopsy, exception may be granted only upon discussion with the principal investigator
- Eligibility of patients receiving medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of GW572016 will be determined following review of their use by the principal investigator; a list of medications and substances known or with the potential to interact with CYP450 isoenzymes is provided in: Cytochrome P-450 Enzymes and Drug metabolism; in: Lacy CF, Armstrong LL, Goldman MP, Lance LL eds; Drug Information Handbook 8TH ed. Hudson, OH; LexiComp Inc. 2000: 1364-1371
- HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with GW572016; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
- Patients requiring oral anticoagulants (coumadin, warfarin) are eligible provided there is increased vigilance with respect to monitoring INR; if medically appropriate and treatment available, the investigator may also consider switching these patients to LMW heparin, where an interaction with GW572016 is not expected
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
- Able to swallow and retain oral medication; alternately, for patients who require feeding via nasogastric tubes or who cannot swallow whole tablets, study entry is allowed by following instructions on drug administration
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or
- Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients who have had prior treatment with EGFR or erbB2 targeting therapies
- Patients may not be receiving any other investigational agents or receiving concurrent anticancer therapy
- Patients with known brain metastases but have remained stable for at least 3 months since completion of radiotherapy or surgery, have no significant neurological deficits, and are off corticosteroids, may be allowed on study; patients with symptomatic brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- Patients with a history of other active malignancy in the past 5 years (with the exception of adequately treated cervical carcinoma in situ and non-melanomatous skin cancers) are excluded
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- History of allergic reactions attributed to compounds of similar chemical or biologic composition to GW572016
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because GW572016 is member of the 4-anilinoquinazoline class of kinase inhibitors with the potential for teratogenic or abortifacient effects; breastfeeding should be discontinued if the mother is treated with GW572016
- HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study
- Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis)
- Concomitant requirement for medication classified as CYP3A4 inducer or inhibitor
Trial locations and contacts
1 site in 1 country.
Canada1 site
Princess Margaret Hospital Phase 2 Consortium
Toronto, Ontario, M5G 2M9
About this study
Official title: A Phase 2 Study of GW572016 in Recurrent and/or Metastatic Adenoid Cystic Carcinoma, and Other EGFR-and/or erbB2-expressing Malignant Tumors of the Salivary Glands
Phase II trial to study the effectiveness of lapatinib in treating patients who have recurrent and/or metastatic adenoid cystic cancer or other salivary gland cancers. Lapatinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the antitumor activity of GW572016 in recurrent and/or metastatic adenoid cystic carcinoma of the salivary glands using objective response rates (partial and complete responses).
SECONDARY OBJECTIVES:
- To determine the duration of objective response, rate and duration of stable disease, progression-free, median and overall survival rates of GW572016 in recurrent and/or metastatic adenoid cystic carcinoma of the salivary glands.
II. To estimate the antitumor activity of GW572016 in other epidermal growth factor receptor (EGFR)- and/or erbB2-overexpressing malignant tumors of the salivary glands using objective response rates (partial and complete responses).
III. To document the safety and tolerability of GW572016 in these patient populations
TERTIARY OBJECTIVES:
- To investigate if differences in baseline levels of EGFR and/or erbB2 expression, and receptor phosphorylation status in tumor specimens predict outcome to therapy.
II. To investigate if the inhibitory effects of GW572016 on EGFR and/or erbB2 pathway activation in tumor specimens correlate with clinical outcome.
III. To determine the steady state levels of GW572016 achieved, and their correlation with clinical and laboratory correlative endpoints.
OUTLINE: This is a nonrandomized, open-label, multicenter study.
Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
Patients are followed for survival
- Conditions
- High-grade Salivary Gland Carcinoma, High-grade Salivary Gland Mucoepidermoid Carcinoma, Low-grade Salivary Gland Carcinoma, Low-grade Salivary Gland Mucoepidermoid Carcinoma, Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Salivary Gland Cancer
- Being tested
- lapatinib ditosylate, laboratory biomarker analysis
- Medical subject headings
- Salivary Gland Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lapatinib ditosylateDrug
Also called GSK572016, GW-572016, GW2016, Lapatinib
Given orally
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (lapatinib ditosylate) | Experimental | Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Receives: Drug: lapatinib ditosylate; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rates (Partial and Complete Responses)
Per Response - Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions;
Measured: Up to 5 years
Secondary outcomes (5)
Duration of Objective Response
Measured: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years
Rate of Stable Disease
Number of patients who had Stable disease for more than or equal to 6 months together in both Adenoid cystic carcinoma (ACC) and non-adenoid cyctic carcinoma (non-ACC)
Measured: 6 months
Progression-free Survival (PFS) According to RECIST
Measured: From the date of study enrolment to disease progression, death or last contact, or last tumor assessment before the start of further anti-tumor therapy, assessed up to 5 years
Overall Survival (OS)
Survival estimates will be computed using the Kaplan-Meier method.
Measured: From the date of study enrolment to death or last contact, assessed up to 5 years
Most Frequent Adverse Events of Grade 1-2 by CTCAE Grading
Number of participants that experienced the most frequent adverse events of grade 1-2 by CTCAE grading.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2004 (estimated)
- Study startSep 2004
- Primary completionFeb 2009
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for High-grade Salivary Gland CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Lillian Siu, Principal investigator, Princess Margaret Hospital Phase 2 Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00095563
- Sponsor's protocol ID
- NCI-2012-03089
- Other IDs
- NCI-2012-03089, 6701, PHL-028, 6701, N01CM62201, N01CM62203
- Status last verified
- Mar 2017
- First submitted
- 5 Nov 2004
- Last updated
- 18 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of GW572016 in Recurrent and/or Metastatic Adenoid Cystic Carcinoma, and Other EGFR-and/or erbB2-expressing Malignant Tumors of the Salivary Glands
- ClinicalTrials.gov ID
- NCT00095563
- Acronym / sponsor ID
- NCI-2012-03089
- Conditions
- High-grade Salivary Gland Carcinoma, High-grade Salivary Gland Mucoepidermoid Carcinoma, Low-grade Salivary Gland Carcinoma, Low-grade Salivary Gland Mucoepidermoid Carcinoma, Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Salivary Gland Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Sep 2004
- Primary completion
- Feb 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 8 Nov 2004 (estimated)
- Results
- Posted 18 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase II trial to study the effectiveness of lapatinib in treating patients who have recurrent and/or metastatic adenoid cystic cancer or other salivary gland cancers. Lapatinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.
Detailed description
PRIMARY OBJECTIVES:
- To determine the antitumor activity of GW572016 in recurrent and/or metastatic adenoid cystic carcinoma of the salivary glands using objective response rates (partial and complete responses).
SECONDARY OBJECTIVES:
- To determine the duration of objective response, rate and duration of stable disease, progression-free, median and overall survival rates of GW572016 in recurrent and/or metastatic adenoid cystic carcinoma of the salivary glands.
II. To estimate the antitumor activity of GW572016 in other epidermal growth factor receptor (EGFR)- and/or erbB2-overexpressing malignant tumors of the salivary glands using objective response rates (partial and complete responses).
III. To document the safety and tolerability of GW572016 in these patient populations
TERTIARY OBJECTIVES:
- To investigate if differences in baseline levels of EGFR and/or erbB2 expression, and receptor phosphorylation status in tumor specimens predict outcome to therapy.
II. To investigate if the inhibitory effects of GW572016 on EGFR and/or erbB2 pathway activation in tumor specimens correlate with clinical outcome.
III. To determine the steady state levels of GW572016 achieved, and their correlation with clinical and laboratory correlative endpoints.
OUTLINE: This is a nonrandomized, open-label, multicenter study.
Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
Patients are followed for survival
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (lapatinib ditosylate) | Experimental | Drug: lapatinib ditosylate, Other: laboratory biomarker analysisPatients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Patients must have histologically documented or cytologically confirmed adenoid cystic, or other malignant salivary gland carcinomas of major or minor salivary gland origin; all patients must have either EGFR and/or erbB2 expressing tumors (for definitions of EGFR and erbB2 expression to be enrolled in this study; EGFR and erbB2 expression will be determined using archival paraffin samples for all study patients where possible; if these samples are unavailable then patients must undergo a biopsy to determine their EGFR and erbB2 status
- Patients must have recurrent and/or metastatic disease that is progressive and not amenable to surgery or curative radiotherapy; progressive disease is defined as one of the following occurring within 6 months of study entry:
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
- Patients may have had unlimited prior therapy; however, there must be at least a 4 weeks' interval between any chemotherapy (6 weeks for nitrosoureas or mitomycin C), radiotherapy or surgery and study enrollment; exceptions may be made however, for low dose, non-myelosuppressive radiotherapy - please contact the Principal Investigator (Dr. L. Siu) PRIOR to registration if questions arise about the interpretation of this criterion; for patients who received local therapy prior to study entry, there must be either progression of measurable disease documented within the treatment field, or must have measurable disease outside the treatment field prior to study entry
- Life expectancy of greater than 12 weeks
Key exclusion criteria (12 listed)
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or
- Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients who have had prior treatment with EGFR or erbB2 targeting therapies
- Patients may not be receiving any other investigational agents or receiving concurrent anticancer therapy
- Patients with known brain metastases but have remained stable for at least 3 months since completion of radiotherapy or surgery, have no significant neurological deficits, and are off corticosteroids, may be allowed on study; patients with symptomatic brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lapatinib ditosylateAlso: GSK572016, GW-572016, GW2016, LapatinibGiven orally | Drug | Treatment (lapatinib ditosylate) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (lapatinib ditosylate) |
Primary outcome
Objective Response Rates (Partial and Complete Responses)
Time frame: Up to 5 years
Per Response - Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions;
5 secondary outcomes
Duration of Objective Response
Time frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years
Rate of Stable Disease
Time frame: 6 months
Progression-free Survival (PFS) According to RECIST
Time frame: From the date of study enrolment to disease progression, death or last contact, or last tumor assessment before the start of further anti-tumor therapy, assessed up to 5 years
Overall Survival (OS)
Time frame: From the date of study enrolment to death or last contact, assessed up to 5 years
Most Frequent Adverse Events of Grade 1-2 by CTCAE Grading
Time frame: Up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lillian Siu principal investigator
Princess Margaret Hospital Phase 2 Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing lapatinib ditosylate and laboratory biomarker analysis in people with High-grade Salivary Gland Carcinoma and High-grade Salivary Gland Mucoepidermoid Carcinoma, run by National Cancer Institute (NCI) at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rates (Partial and Complete Responses) (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2017; AzTrials last refreshed its copy on 7 Nov 2026.